Fields of Research

• Opioid receptor signal transduction mechanisms;
• Neuropetide electrophysiology physiology;
• Tolerance and receptor desensitization mechanisms;
• Neurocircuits controlling motivated behaviors;
• Stress mechanisms controlling drug addiction and depression risk

Research Summary

If it’s not norBNI sensitive, honey badgers don’t care.

Research Statement

We are interested in the molecular basis of drug addiction. Drugs including heroin, cannabinoids, cocaine, and others produce specific pharmacological effects that ultimately change the functioning of neurons, reorganize plastic neural circuits, and change motivated behavior. In this lab, we take an integrative, neurobiological approach to define these changes at the molecular, cellular, anatomical and behavioral levels. Studies at the molecular level define the structural properties of the receptors and ion channels that mediate the initial actions of opiates and cannabinoids. We are interested in learning how signaling events initiated by receptor activation are regulated, and how receptors, channels, and accessory proteins assemble to form functional macromolecular complexes. At the cellular level, we study how sustained exposure to opiates produces desensitization and how phosphorylation, down regulation, and synaptic plasticity (LTP and LTD) mechanisms contribute to drug tolerance. At the anatomical level, we study the distribution of the key proteins within brain that are important for opiate action and how that distribution helps define the neuronal systems responsible for drug effects. Understanding how that distribution changes following repeated drug exposure helps define the changes underlying drug addiction. Based on these cellular and molecular insights, we generate mice having targeted changes in gene expression of key proteins in specific brain regions, and then study the behavioral responses of the animals to opiates and cocaine. The ultimate goal of these studies is to gain a better understanding of the molecular basis of drug addiction, a malleable form of motivated behavior.

Awards and Honors

Honors:

Cornelius Wiersma Visiting Professorship of Neurosciences at the California Institute of Technology 9/92-7/93
Elected as President of the International Narcotics Research Conference, 1998-2002
UW “Science in Medicine Lecture” – 2/10/00
UW “Science Forum Lecture” – 3/7/03
July 2004 named by the Dean of Medicine as the “Allan and Phyllis Treuer Endowed Chair in Pain Research”
MERIT award from National Institute on Drug Abuse, 3/05
K05 Senior Scientist & Mentoring Award from National Institute on Drug Abuse, 9/06
Elected AAAS-Fellow (Pharmaceutical Sciences), 11/06
Elected member American College of Neuropsychopharmacology (ACNP) (12/06)
advanced to ACNP-Fellow (12/11)
“2011-INRC Founders’ Lecture” 6/2011
Elected Member of the Washington State Academy of Sciences (July 2012)
Kang Tsou Memorial Lecture, International Cannabinoid Society (ICRS) Vancouver, BC (June 2013)
University of Pennsylvania Louis B. Flexner Lecture (2017)
Current Awards:

NIH/NIDA R01 DA030074-09: p38 MAPK Mechanisms of Kappa Opioid-Induced Aversion. C. Chavkin, PI
Period: 3/2011 – 6/2021
Description: The goal of this project is to understand how activation of p38 MAPK by KOR stimulation, either by stress-induced dynorphin release in the dorsal raphe nucleus or systemic administration of a selective KOR agonist, results in conditioned place aversion. This award supports ongoing studies of the signal transduction events linking kappa receptor activation to p38a MAPK activation. It further supports studies using in vivo fast scan cyclic voltammetry to define the effects of KOR-p38 of dopamine release and reuptake mechanisms. This award is focused on stress effects on signaling in DRN, VTA and NAc as a risk of developing drug addiction.
NIH/NIDA P30 DA048736-01: “University of Washington Center of Excellence in Opioid Addiction Research” Chavkin, PI
Period: 07/2019-06/2024
Description: The P30 provides access to state-of-the-art in vivo imaging equipment, viral production facilities (viral & CRISPR reagents), and training. This program project grant is designed to provide shared resources that enhance the efficiency and facilitates collaborative research for the study of the effects of opioids on neural circuits with the goal of understanding opioid addiction mechanisms and developing novel treatments for drug addiction. In addition to the Administrative and Pilot Project Cores, the Center includes an Imaging and Neural Circuits Core and Molecular Genetics Resource Core. All of these components are focused on facilitating research designed to understand the changes in neural circuitry responsible for opioid addiction and on the development of new therapeutic tools based on these insights. Co-PIs include Drs. Susan Ferguson, Michael Bruchas, Garret Stuber and Larry Zweifel.